Cyclin E Expression and p16 Loss Are Strong Prognostic Biomarkers in Primary Invasive Cutaneous Melanoma

Abstract

Background/aim: The traditional melanoma staging system is not ideal for predicting patients' individual risk of disease recurrence and death. Subsequently, suboptimal adjuvant treatment may be offered. Hence, identification of biomarkers to optimize risk stratification is warranted. Cyclins and cyclin-dependent kinase inhibitors, key players in the cell cycle regulation, are candidate prognostic biomarkers. Herein, their expression and prognostic value in melanoma are studied.

Patients and methods: The expression of Cyclin D1, Cyclin E, p16, p21, and p27 were assessed using immunohistochemistry in samples from 59 patients with melanoma and correlated with clinicopathological parameters, as well as relapse-free survival (RFS) and overall survival (OS).

Results: Cyclin E expression in the nucleus, observed in 19% of patients, was correlated with Breslow thickness (p=0.017), whereas p16 loss in the cytoplasm and nucleus, detected in 68% and 61% of patients respectively, was correlated with Breslow thickness (p=0.001) and ulceration (p=0.035). The high expression of Cyclin E in the nucleus (p<0.001) and the loss of p16 in the cytoplasm (p=0.012) and nucleus (p=0.002) were associated with shorter OS. Cyclin E in the nucleus was a prognostic factor for RFS and OS at least as strong as Breslow thickness.

Conclusion: Expression of Cyclin E and loss of p16 appeared to be significant prognostic biomarkers, with Cyclin E being prognostically at least as strong as Breslow thickness regarding RFS and OS. Both biomarkers may potentially be used to improve stratification of individual patient's risk of recurrent disease and survival, and subsequently optimize adjuvant treatment.

Keywords: Cyclin D1; Cyclin E; Melanoma; cyclin-dependent kinase inhibitors; cyclins; p16; p21; p27; prognostic biomarkers.